rs3897937

Variant names:

• chrX-50912016-A-G
• rs3897937
• NM_005448.2:c.328+905A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-50912016-A-G
• chrX-50912016-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005448.2(BMP15):​c.328+905A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 110,206 control chromosomes in the GnomAD database, including 6,864 homozygotes. There are 11,507 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (6864 hom., 11507 hem., cov: 22)
• Consequence: BMP15 NM_005448.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266
• Publications: 11 publications found

Genes affected

BMP15 (HGNC:1068): (bone morphogenetic protein 15) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate subunits of a disulfide-linked homodimer, or alternatively, a heterodimer, with the related protein, growth differentiation factor 9 (GDF9). This protein plays a role in oocyte maturation and follicular development, through activation of granulosa cells. Defects in this gene are the cause of ovarian dysgenesis and are associated with premature ovarian failure. [provided by RefSeq, Aug 2016]

BMP15 Gene-Disease associations (from GenCC):

• ovarian dysgenesis 2

  Inheritance: XL, AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 46 XX gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP15	NM_005448.2	c.328+905A>G		intron_variant	Intron 1 of 1	ENST00000252677.4	NP_005439.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP15	ENST00000252677.4	c.328+905A>G		intron_variant	Intron 1 of 1	1	NM_005448.2	ENSP00000252677.3

Frequencies

GnomAD3 genomes AF: 0.373 AC: 41101 AN: 110153 Hom.: 6855 Cov.: 22

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.0912

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.314

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.324

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.373 AC: 41147 AN: 110206 Hom.: 6864 Cov.: 22 AF XY: 0.354 AC XY: 11507 AN XY: 32508

African (AFR) AF: 0.646 AC: 19453 AN: 30103

American (AMR) AF: 0.215 AC: 2227 AN: 10374

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 785 AN: 2624

East Asian (EAS) AF: 0.0910 AC: 322 AN: 3540

South Asian (SAS) AF: 0.326 AC: 829 AN: 2543

European-Finnish (FIN) AF: 0.218 AC: 1277 AN: 5848

Middle Eastern (MID) AF: 0.324 AC: 70 AN: 216

European-Non Finnish (NFE) AF: 0.294 AC: 15505 AN: 52786

Other (OTH) AF: 0.323 AC: 483 AN: 1497

Alfa AF: 0.327 Hom.: 23826

Bravo AF: 0.381

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.51
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3897937; hg19: chrX-50655016;